Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model

Jiuqing Lu,1,2,* Nijia Yu,1,* Qian Liu,2,* Yajia Xie,1 Lei Zhen2 1Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Stomatology, Tongji Hospital, School of Medicine, Tongji Universi...

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Main Authors: Lu J, Yu N, Liu Q, Xie Y, Zhen L
Format: Article
Language:English
Published: Dove Medical Press 2023-09-01
Series:International Journal of Nanomedicine
Subjects:
Online Access:https://www.dovepress.com/periodontal-ligament-stem-cell-exosomes-key-to-regulate-periodontal-re-peer-reviewed-fulltext-article-IJN
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author Lu J
Yu N
Liu Q
Xie Y
Zhen L
author_facet Lu J
Yu N
Liu Q
Xie Y
Zhen L
author_sort Lu J
collection DOAJ
description Jiuqing Lu,1,2,* Nijia Yu,1,* Qian Liu,2,* Yajia Xie,1 Lei Zhen2 1Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Stomatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zhen, Department of Stomatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Tel +86 1 582 108 9038, Email zhenleilei123@126.comIntroduction: Periodontitis is a chronic inflammatory disease that causes alveolar bone loss. Diabetes is one of the most important factors contributing to periodontitis. Exosomes derived from mesenchymal stem cells (MSCs-Exo) have been reported to promote bone regeneration. This study aimed to examine the function and mechanism of exosomes derived from periodontal ligament stem cells (PDLSCs-Exo) in regulating periodontal regeneration in diabetic periodontitis.Methods: Exosomes derived from normal-glucose-cultured PDLSCs (NG-PDLSCs-Exo) and high-glucose-preconditioned PDLSCs (HG-PDLSCs-Exo) were used. Their effects on RAW264.7 cells were investigated by TRAP staining and quantitative real time-polymerase chain reaction (qRT-PCR). The role of exosomal miR-31-5p in osteoclast differentiation was tested using qRT-PCR, double luciferase analysis, and Western blotting. We investigated the effects of these two types of PDLSCs-Exo on alveolar bone loss in vivo in mice with experimental periodontitis.Results: PDLSCs-Exo were transferred to RAW264.7, and HG-PDLSCs-Exo inhibited osteoclast formation to a lesser extent than NG-PDLSCs-Exo. Further studies revealed the effect of PDLSCs-Exo on osteoclastogenesis via the miR-31-5p/eNOS signaling pathway. In mice with experimental periodontitis, PDLSCs-Exo reduced alveolar bone destruction and decreased the number of osteoclasts on the alveolar bone surface.Conclusion: Our results suggest that exosomal miR-31-5p derived from PDLSCs regulates alveolar bone regeneration by targeting eNOS.Keywords: diabetes, periodontitis, macrophage, osteoclast differentiation
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spelling doaj.art-a739e6f4ab814fcd80ca384735e013e72023-09-21T19:08:58ZengDove Medical PressInternational Journal of Nanomedicine1178-20132023-09-01Volume 185327534286743Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice ModelLu JYu NLiu QXie YZhen LJiuqing Lu,1,2,* Nijia Yu,1,* Qian Liu,2,* Yajia Xie,1 Lei Zhen2 1Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Stomatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zhen, Department of Stomatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Tel +86 1 582 108 9038, Email zhenleilei123@126.comIntroduction: Periodontitis is a chronic inflammatory disease that causes alveolar bone loss. Diabetes is one of the most important factors contributing to periodontitis. Exosomes derived from mesenchymal stem cells (MSCs-Exo) have been reported to promote bone regeneration. This study aimed to examine the function and mechanism of exosomes derived from periodontal ligament stem cells (PDLSCs-Exo) in regulating periodontal regeneration in diabetic periodontitis.Methods: Exosomes derived from normal-glucose-cultured PDLSCs (NG-PDLSCs-Exo) and high-glucose-preconditioned PDLSCs (HG-PDLSCs-Exo) were used. Their effects on RAW264.7 cells were investigated by TRAP staining and quantitative real time-polymerase chain reaction (qRT-PCR). The role of exosomal miR-31-5p in osteoclast differentiation was tested using qRT-PCR, double luciferase analysis, and Western blotting. We investigated the effects of these two types of PDLSCs-Exo on alveolar bone loss in vivo in mice with experimental periodontitis.Results: PDLSCs-Exo were transferred to RAW264.7, and HG-PDLSCs-Exo inhibited osteoclast formation to a lesser extent than NG-PDLSCs-Exo. Further studies revealed the effect of PDLSCs-Exo on osteoclastogenesis via the miR-31-5p/eNOS signaling pathway. In mice with experimental periodontitis, PDLSCs-Exo reduced alveolar bone destruction and decreased the number of osteoclasts on the alveolar bone surface.Conclusion: Our results suggest that exosomal miR-31-5p derived from PDLSCs regulates alveolar bone regeneration by targeting eNOS.Keywords: diabetes, periodontitis, macrophage, osteoclast differentiationhttps://www.dovepress.com/periodontal-ligament-stem-cell-exosomes-key-to-regulate-periodontal-re-peer-reviewed-fulltext-article-IJNdiabetesperiodontitismacrophageosteoclast differentiation
spellingShingle Lu J
Yu N
Liu Q
Xie Y
Zhen L
Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model
International Journal of Nanomedicine
diabetes
periodontitis
macrophage
osteoclast differentiation
title Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model
title_full Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model
title_fullStr Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model
title_full_unstemmed Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model
title_short Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model
title_sort periodontal ligament stem cell exosomes key to regulate periodontal regeneration by mir 31 5p in mice model
topic diabetes
periodontitis
macrophage
osteoclast differentiation
url https://www.dovepress.com/periodontal-ligament-stem-cell-exosomes-key-to-regulate-periodontal-re-peer-reviewed-fulltext-article-IJN
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